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Genomic Based Drug Discovery

 

Executive Summary

The Broad Institute has assembled an Interdisciplinary Research Consortium with the goal of developing a new paradigm for drug discovery and development that begins and ends with patients. The Consortium draws from advances in human biology (especially genetics and physiology) and combines novel chemicals (small molecules) with innovative high-throughput screening methods that focus on how these molecules affect cells and organisms. These effects are either phenotypic (how the cells look or behave), or genetic (what genes the cells express). Additional methods have been developed to help researchers identify the mechanism-of-action of these small molecules and to reveal potential toxicity issues early in the development cycle. These techniques are being used to identify potential new therapeutics for cancer, psychiatric disease, and other complex medical conditions.

Consortium Director and Scientists

Scherer, Christina, 5UL1DE019585-04: GENOMICS BASED DRUG DISCOVERY
Golub, Todd, 1RL1CA133834-01: DISCOVERY PIPELINE
Schreiber, Stewart, 1RL1HG004671-01: TARGET ID
Scolnick, Edward, 1RL1GM084437-01: DRIVING MEDICAL PROJECTS
 

Selected Publications

  1. Raj L, Ide T, Gurkar AU, Foley M, Shenone M, Li X, Tolliday NJ, Golub TR, Carr SA, Shamji AF, Stern AM, Mandinova A, Schreiber SL, and Lee SW. Selective killing of cancer cells by a small molecule targeting the stress response to ROS. Nature 2011; 475(7355):231-4. PMID: 21753854.
     
  2. Fomina-Yadlin D, Kubicek S, Walpita D, Dančík V, Hecksher-Sørensen J, BittkerJA, Sharifnia T, Shamji A, Clemons PA, Wagner BK, and Schreiber SL. Small molecule inducers of insulin expression in pancreatic alpha cells. (2010) Proc. Natl. Acad. Sci. USA 107:15099-15104. PMID: 20696901.
     
  3. Comer E, Liu H, Joliton A, Clabaut A, Johnson C, Akella LB, and Marcaurelle LA. Organic Synthesis Toward Small-Molecule Probes and Drugs Special Feature: Fragment-based domain shuffling approach for the synthesis of pyranbased macrocycles. (2011) Proc. Natl. Acad. Sci. U S A. Mar 7 [Epub ahead of print]. PMID: 21383141.
     
  4. Pan JQ, Lewis MC, Ketterman JK, Clore EL, Riley M, Richards KR, Berry-Scott E, Liu X, Wagner FF, Holson EB, Neve RL, Biechele TL, Moon RT, Scolnick EM, Petryshen TL, and Haggarty SJ. AKT Kinase Activity Is Required for Lithium to Modulate Mood-Related Behaviors in Mice. Neuropsychopharmacology. (2011) Mar 9. [Epub ahead of print]. PMID:21389981
     
  5. Kuai, L, Ong, S.E., Madison, J.M., Wang, X, Duvall, J.R., Lewis, T.A., Luce,C.J., Conner, S.D., Pearlman, D.A., Wood, J.L., Schreiber, S.L., Carr, S.A., Scolnick, E.M. and Haggarty, S.J. (2011). Identification of AAK1 as an Inhibitor of Neuregulin-1/ErbB4-Dependent Neurotrophic Factor Signaling Using Integrative Chemical Genomics and Proteomics. (2011) Chemistry & Biology. (in press).

 

 

 

 

 

 

Genomic Based Drug Discovery Scientists

Genomic Based Drug Discovery Scientists. Top row, from left: Edward Scolnick, M.D., Todd Golub, M.D; bottom row: Stewart Schreiber, Ph.D., Christina Scherer, Ph.D.
 

Genomic Based Drug DiscoveryImmunofluorescent images showing reprogramming of adult mouse pancreatic acinar cells to beta cells.
Image depicts Genomic Based Drug
Discovery Research Diagram

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